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Biomedical subjects

M D Walker

Publications and source records attributed to M D Walker.

At least 91 records · Page 5Linked to original sources
PubMed1980

Misonidazole peripheral neuropathy: its relationship to plasma concentration and other drugs.

The data from 44 patients with documented glioblastoma who received 1.5 g/m2 of misonidazole twice weekly in conjunction with whole brain radiotherapy (total dose 6000 rad) was analyzed for factors associated with the development of peripheral neuropathy. The average total cumulative dose of misonidazole was 16.9 g/m2 and mild to moderate reversible peripheral neuropathy developed in 18% of patients. Peripheral neuropathy was positively associated with: 1) evidence of residual misonidazole in pretreatment plasma samples (> 10 microgram/ml), 2) elevated plasma concentrations of misonidazole on the day following treatment (> 25% of 4-hour plasma concentration), and 3) a prolonged plasma half-life (an average of 25% greater in patients developing peripheral neuropathy). The use of corticosteriods was negatively associated with the development of peripheral neuropathy and appeared to confer some protection. Age, sex, total dose of misonidazole, 4-hour plasma concentration (namely, at the time of radiotherapy), or the receipt of phenytoin or barbiturates was not related to the development of peripheral neuropathy. Monitoring of plasma misonidazole concentrations during treatment in conjunction with careful examination of the patient may result in a reduction of the incidence or severity of peripheral neuropathy.

Adrenal Cortex Hormones↗
PubMed1978

Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial.

A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.

Adolescent↗
PubMed1977

Synthesis of tubulin and actin by neuronal and glial nuclear preparations from devloping rat brain.

A system was established in which nuclear preparations from rat brains were capable of protein synthesis under cell-free conditions. The electrophoretic pattern of the synthesized proteins was similar to that found in vivo provided that the reaction mixture contained pH 5 precipitated factors derived from the high speed supernatant fraction of brain. In the absence of the pH 5 factors, using nuclear preparations from brains of 2-day-old rats, approximately 1.5% and 2% of the newly synthesized proteins were identified as tubulin and actin, respectively. In the presence of pH 5 factors, protein synthesis was stimulated and the proportion of the newly synthesized tubulin and actin increased to 26% and 11%, respectively. In contrast to nuclear fractions from 2-day-old rats, when nuclei from brains of 1-month-old rats were tested in the presence of pH 5 factors, the proportion of tubulin and actin synthesized was lower and amounted to 10% and 4%, respectively. The age-dependent change in the relative amount of the tubulin and actin synthesized is in good agreement with the translational pattern shown by brain polyribosomes in a brain cell-free system as well as with the pattern obtained with brain mRNA translated in a wheat germ cell-free system. Nuclei enriched for either neuronal or glial populations synthesized similar proportions of tubulin and actin in vitro. We conclude that the reduction in the synthesis of tubulin and actin during the postnatal development of the rat brain occurs in both neuronal and glial cells.

Actins↗
PubMed1977

Brain Tumor Study Group: a survey of current activities.

Improvement in the treatment of patients harboring malignant glioma will probably be seen as small incremental changes as new modalities of treatment are proposed, tested, and substantiated. Uncontrolled phase II studies may provide hints of efficacy. However, the results must be substantiated in carefully controlled phase III evaluations. The Brain Tumor Study Group of the National Cancer Institute has demonstrated that mithramycin is not effective in the treatment of malignant glioma and the overall median survivorship experience is no different than the 23 weeks found in historic controls. Radiotherapy can bring about a meaningful increase in survival as can 1,3-bis(2-chloroethyl)-1-nitrosourea. The combination appears to produce more long-term survivors than either treatment above. Methyl-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea does not appear to be additive to radiotherapy but is more effective than no therapy at all. Studies of the oncolytic effect of corticosteroids in contradistinction to their cerebral edema controlling effects are being done and will provide meaningful data on this important symptomatolytic therapy.

Brain Neoplasms↗
PubMed1977

Prognostic factors for patients with brain tumors.

Patient characteristics of 225 patients entered into a clinical trial conducted by the Brain Tumor Study Group (69-01) were examined for their relationship to survival time. In the clinical study, all patients received surgery and were randomized to control treatment (no further treatment), X-ray therapy (XRT), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), or BCNU + XRT. When treatment was considered as a possible prognostic factor, the patient characteristics most related to survival were: XRT (receiving XRT favorable), age (young, favorable), symptoms of seizures and cranial nerves (both favorable), BCNU treatment (yes, favorable), encapsulated tumor (yes, favorable), and parietal tumor (no, favorable). When treatment was not considered a possible prognostic factor, the patient characteristics most related to survival were: age (young, favorable), biopsy (operation biopsy only, unfavorable), seizures (yes, favorable), cranial nerve symptoms (yes, favorable), and parietal location of tumor (yes, unfavorable). Knowledge of prognostic factors can be used for stratifying patients in clinical studies, for testing the comparability of groups of patients, and in the analysis of the results of clinical studies.

Age Factors↗